It is generally recognized that smoking, particularly cigarette smoking, is a prime cause of vascular disorders, lung and oral cancer, and cancer of the upper respiratory tract. It is known that tobacco smoke contains cancer-causing agents and that these agents are carried to the smoker's mouth and respiratory tract in the tobacco smoke. It is also known that certain biologically active or drug materials known as biological response modifiers (BRM), including retinoids (vitamin A and its natural and synthetic analogs), thymosin, the interferons, and others, have been shown to have the ability to prevent or modify carcinogen-induced animal and human cancers. These compounds have the ability not only to modify or inhibit the growth of existing cancers, but also to block the induction of cancer, i.e., to act as cancer chemopreventive agents. In addition, a potentially useful method of reducing harmful cigarette smoke inhalation involves the oral delivery of nicotine from a reduced-smoke or "smokeless" cigarette, thus satisfying the physiologic need for nicotine while preventing the ingestion of harmful smoking-related carcinogens and irritants. Furthermore, no general drug delivery system is presently available which can provide controlled dosages of orally-active drugs using cigarette smoking as the delivery medium.
In order to take advantage of the apparent cancer-preventive properties of vitamin A and its analogs, it has been proposed to provide cigarettes with a filter incorporating a supply of these materials. In U.S. Pat. No. 3,339,558, vitamin A is contained within a rupturable capsule which is ruptured by the smoker immediately prior to smoking. U.S. Pat. No. 3,525,582 shows a similar cigarette in which vitamin A is encapsulated in a heat rupturable capsule, which is ruptured by the heat of the burning tobacco. In U.S. Pat. No. 3,667,478, a stabilized form of vitamin A, capable of withstanding long periods of storage, is distributed throughout the filter, rather than being contained in a separate capsule. European Patent Application No. 0 003 064 A2 shows a similar cigarette in which certain synthetic vitamin A analogs are used as the biologic response modifier.
In all of the above-mentioned cigarettes, the vitamin A or other BRM or drug is deposited on the filter material (or the tobacco when no filter is used) adjacent the end of the cigarette held in the mouth of the smoker. During smoking, the drug is entrained within the concentrated stream of tobacco smoke passing through the cigarette and is carried into the mouth of the smoker. The drug is, therefore, exposed within the cigarette itself to the hot concentrated stream of smoke, creating the possibility of thermal degradation of the drug substance as well as adverse chemical reactions with the active ingredients of the tobacco smoke.